October 29-November 1Gaylord National Harbor • National Harbor, MD

[R5] Biosimilars in the United States: Barriers, Solutions, Real-World Evidence, and the

Experience of One Health System

Gillian Woollett, MA, DPhilSenior Vice President, Avalere Health

Cate Lockhart, MS, PharmD, PhDExecutive Director, BBCIC

Molly Leber, PharmD, BCPS, FASHPAssociate Director, Drug Use Policy and Formulary,

Yale New Haven Health System

Learning Objectives

1. Describe the current approval and marketing status of biosimilars in the United States.

2. Recognize lingering barriers to uptake and utilization of biosimilars.3. Explain the role of real-world evidence in supporting biosimilar

utilization.4. Discuss the experience of one hospital where biosimilars are being

used.

Instructional Slide

• AMCP will add Housekeeping slides related to learning objectives, full faculty information, financial disclosures, ACPE info, audience polling instructions, etc

• Moderator will be covering these housekeeping slides

PRE-TEST

LQ1: Of the 23 biosimilars that have been approved in the U.S. to date, how many are available on the market?

a) 4b) 9c) 17d) 23

LQ2: Among U.S. prescribers in specialties where biologics are frequently prescribed, what is the percent who trust biosimilars are safe?

a) Between 10% and 20%b) Between 40% and 50%c) Between 60% and 70%d) Between 80% and 90%

LQ3: All of the following are limitations of commonly-used real-world data sources, EXCEPT:

a) Data are typically collected for reasons other than researchb) Market uptake may influence research capabilitiesc) Clinical effectiveness outcomes may be challenging to identifyd) Data are usually randomized

LQ4: Which is a barrier to biosimilar adoption within a hospital system?

a) Ongoing litigation prevents access to biosimilarsb) Uncertainty around reimbursementc) Design of novel delivery technologyd) Both a and be) All of the above

Agenda

• Biosimilars in the United States: current status• Barriers to Biosimilar Utilization• Real-World Evidence• Yale New Haven Health System: Biosimilars in Practice

The Mountainous Challenges for Biosimilars in the US

USA 23 approvals 9+ (unclear) 9 launches

FDA Approval Exclusivity and IP Commercialization

FDA approval is the first of a series of challenges

Time

Cos

t

Can there be a sustainable multisource specialty market in the US?

Biotech Approvals Have Increased and are Expected to Rise

1. FDA. “Drug and Biologic Approval Reports.” Not including vaccines and blood products http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/default.htm

2. PhRMA. “Biotechnology Research Promises to Bolster the Future of Medicine with More Than 900 Medicines and Vaccines in Development.” 2013. http://www.phrma.org/sites/default/files/pdf/biologics2013.pdf

The science is the best it has even been; biotech is offering wholly new approaches to unmet medical needs. Competition based on value is key

0

2

4

6

8

10

12

14

16

18

20

22

24

26

Non-orphan Orphan Biosimilar

Approvals (NDA & BLA)

0

100

200

300

400

500

600

700

800

900

1000

In Development (NDA & BLA)

In Development (NDA & BLA)

• VALUE IS A COMBINATION OF CLINICAL OUTCOME AND PRICE

Context: Public Recognition of Value of Biopharmaceuticals

Perception of Usurious Price

TimeBiosimilar Approval(s)

$HEALTHY PRICE BASED ON VALUE

Uneconomic to Produce

Perception of Usurious Price

Originator Biologics Price Trends

To moderate prices mechanisms are needed to support competition amongst biologics irrespective of the regulatory pathway by which they are approved

Avalere Analysis of Medicare Part B and D Drug Spending Data. Available on CMS website: https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/Information-on-Prescription-Drugs/MedicarePartB.html.

Avalere: Five Obstacles to Competition, 31May17 http://avalere.com/expertise/life-sciences/insights/five-obstacles-to-competition-in-the-united-states-biologics-market

• In 2016, biologics made up 91% of spending on the top 20 Part B

US Biologics Market – Large and Increasing

$10.5$11.0

$12.1$12.8

$14.5$15.3

$6.8$7.7

$8.9$9.7

$11.5

$13.9

$3.7 $3.3 $3.2 $3.1 $3.0

$1.4$0

$2

$4

$6

$8

$10

$12

$14

$16

$18

2011 2012 2013 2014 2015 2016

Spen

ding

($ B

illion

s)

Total Spend in the Top 20 Biologics in the Top 20 All Other Drugs in the Top 20

Obstacles to creating a multi-source biologics environment include complexity of development, prescribing patterns, interchangeability, physician reimbursement models, and payer coverage

1. Newly Added Guidance Documents here; 2. New steps FDA is taking to enhance transparency of clinical trial information to support innovation and scientific inquiry related to new drugs here; 3. product quality and transparency at foreign drug manufacturing facilities here; 4. Preparations for the upcoming flu season and vaccinations here; 5. policy steps and enforcement efforts to ensure proper oversight of stem cell therapies and regenerative medicine here; 6. Why Scott Gottlieb is the one Trump official everybody seems to like here; 7. FDA Reorg here

Dr. Gottlieb was only the Commissioner. He had to persuade those with power to implement change and make it stick. That was tested by his leaving

What has actually happened:

• Huge uptick in the number of FDA guidances issued1, and other initiatives: Clinical trials transparency2

including global initiatives3

• Much higher visibility for the FDA, from flu vaccines4 to cell therapy5

• Addiction dominating headlines (nicotine and opioids)

• USG Shut down, yet many initiatives sped up, e.g. complex generics, compounding

• FDA, especially Dr. Gottlieb, had the confidence of the Administration, but very high pressure to deliver6;

• Dr. Gottlieb left; FDA Reorganization on 31Mar20197

• Statements and tweets from Dr. Gottlieb every day

What has happened recently at FDA more broadly…

FDA with Dr. Gottlieb was no longer solely domestic nor just about approvals - he was forthright about economics and access; Ned Sharpless from NCI is less well known

• Trump Administration’s “American Patients First” 1 July18 targets lower prices

• The FDA’s Biosimilar Action Plan (BAP) issued Jul182 with a Public Meeting Sept18 and associated docket3. Broad and general goals

• FDA 2019 Biosimilar Guidances4

• Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations; Draft Guidance for Industry, May 2019

• Considerations in Demonstrating Interchangeability With a Reference Product; Guidance for Industry, May 2019

• Staff changes in the Biosimilar Product Development Team at FDA under Congressionally endorsed FDA reorganization, but key appointments are Acting

• Rollover of those biologics regulated as drugs 23Mar2020, including Insulin – new guidance5

Biosimilars have had the Attention of the Trump Administration

1. HHS Blueprint to Lower Drug Prices and Reduce Out-of-Pocket Costs16Jul18 here; 2. BAP 1Jul18 here; 3. Docket here; 4. FDA Biosimilar Guidance's here ; 5. FDA “Deemed to be a License” Provision of the BPCI Act here

Biosimilars appear stuck in the regulatory weeds at FDA – no real focus on consistency in application of regulatory science to all biologics

A MASSIVE FLURRY OF ANNOUNCEMENTS BUT MUCH LESS CHANGE IN POLICY SUPPORT

• https://www.biopharma-reporter.com/Article/2019/01/07/The-impact-of-biosimilars-in-2018

• https://www.nbcnews.com/nightly-news/video/world-s-best-selling-drug-costs-five-times-more-in-u-s-than-europe-1445064259924

2018 saw an increase in the number of biosimilar approvals, and the expiry of patents on major products that allowed the entry of biosimilars across Europe.

07Jan19 By Ben Hargreaves

The impact of biosimilars in 2018: ‘Treating a third more people, at half the cost’1

Europe seems to be Succeeding...US not so much...

The US is the biggest market and yet struggling the most. This simply doesn’t add up, or does it...

WORLD’S BEST-SELLING DRUG COSTS FIVE TIMES MORE IN US THAN EUROPE2

Critics accuse the maker of Humira of exploiting U.S. patent laws to keep competitors’ less expensive versions off the market. The company, AbbVie, says it’s balancing the need to keep the drug affordable to patients with the need to fund new drug development.

19Feb19

NBCNEWS

Europe and the US still have different biosimilar approvals

BioWorld Will price competition follow in the wake of incoming U.S. biosimilar wave? http://www.bioworld.com/content/will-price-competition-follow-wake-incoming-us-biosimilar-wave-0 (accessed 21Jun18)

YET US AND EUROPE ARE THE MOST HARMONIZED REGULATORILY

Requirements for different data in different regions are a problem and not scientifically justified – especially reference product

• http://biosimilarsforum.org/PDF/BIosimilars_WhitePaper-final.pdf

• IMS Health MIDAS MAT Q4 2016 - [$1,844,857,846 out of $246,643,913,154]

• Worldwide Biosimilars STILL Face Considerable Challenges1

Global Sales by % Total Market for Biologics & Biosimilars

Biosimilar sales globally under 1 percent of those of originator biologics worldwide, so the room for further savings remain large and apply in, as well as well beyond, the US and Europe.

The global drivers for biologics competition are increasingly crucial for access worldwide.... AND for access in the US

Created through discussions with Ken Williams, Avalere

1. Demonstration of Comparability of Human Biological Products, Including Therapeutic Biotechnology-derived Products April 1996 here

• Scientific and regulatory principles are established FOR ALL BIOLOGICS – ESPECIALLY IN THE US Consistent APPLICATION REMAINS A HUGE CHALLENGE

The Name Does Not Change The Product in the Tube

Presumed problem

Actualproblem

Without the message that the reference products vary too, biosimilars will continue to struggle to succeed in the US

Biosimilar

Standards Support Regulatory Decisions Worldwide

1. https://www.azbio.org/small-molecules-large-biologics-and-the-biosimilar-debate2. https://www.gene.com/stories/similar-not-the-same-the-road-ahead-for-biosimilars?topic=oncology

But the wheels on those bicycles, cars and planes are equally round; complexity is not relevant. NO NEED FOR EACH BIOLOGIC SPONSOR TO KEEP REINVENTING THE WHEEL

MANUFACTURING MUST BECOME MORE EFFICIENT IF MEDICINES ARE TO BE AFFORDABLE AND THEREFORE ACCESSIBLE

AZBIO Genentech

Biologic Trade name Sponsor

Countries in which 1st

approvals were based on the same studies

Studies submitted for 1st approvals in > 1

countryIndications studied

Infliximab Remicade Janssen US, EU, Canada, Australia T16, T21 Crohn’s diseaseEtanercept Enbrel Amgen US, EU, Canada, Australia 16.009, 16.014 Rheumatoid arthritis

Adalimumab Humira AbbVie US, EU, Canada, Australia DE009, DE011, DE019, DE031 Rheumatoid arthritis

Pegfilgrastim Neulasta Amgen US, EU, Canada, Australia 980226, 990749Febrile neutropenia in

treatment of non-myeloidcancers

Bevacizumab Avastin Genentech/Roche US, EU, Canada, Australia AVF2107g, AVF0780g Metastatic colon cancer

Ranibizumab Lucentis Genentech US, EU, Canada, Australia FVF2598g, FVF2587g,FVF3192g

Age-related maculardegeneration

*This is not necessarily a comprehensive list of the countries in which these studies were submitted for licensure of the product

• GOAL: Minimize repetitive studies that provide no new data – lack scientific & ethical validity

The Reference is Global, the Biosimilars Needs to be too

Same Registration Studies = Same Clinical Trials Material = Same Approved ProductChristopher J. Webster, Gillian R. Woollett (2017), “A ‘Global Reference’ Comparator for Biosimilar Development”. BioDrugs doi:10.1007/s40259-017-0227-4 http://link.springer.com/article/10.1007%2Fs40259-017-0227-4

1. Medicines for Europe, 16th Biosimilars Mtg, London 26-27 April 2018; 2. Pekka Kurki et al, Interchangeability of Biosimilars: A European Perspective BioDrugs, DOI 10.1007/s40259-017-0210-0; 3. Managed Care Magazine, FDA’s Gottlieb Aims To End Biosimilars Groundhog Day, 25Jan19, https://www.managedcaremag.com/archives/2019/1/fda-s-gottlieb-aims-end-biosimilars-groundhog-day; 4. Hillel P. Cohen et al Switching Reference Medicines to Biosimilars: A Systematic Literature Review of Clinical Outcomes Drugs. https://link.springer.com/article/10.1007/s40265-018-0881-y

Interchangeability as a formal designation – Unique to US Law Dr. Leah Christl, while at FDA, said1 that FDA agrees with the European regulators’ conclusion that biosimilars are interchangeable with their reference2 for the purpose of physician prescribing.

However, she then explained in some detail that interchangeability in the US is a designation solely for the purposes of substitution by other than the prescriber. And for such pharmacist substitution the law was clear that an additional designation from FDA was available.

This FDA designation will confirm there being no basis for switching being a safety or efficacy concern3. Data showing a problem does not exist4

Semantics matter. Nonetheless regulatory consistency is essential to the future potential for harmonization

• Clinical studies that are unnecessary are ALWAYS unethical• Meaningful data is way more than reassuring data, or nice to

know – it is essential data

• All clinical studies are a tax on patients and must add value

Harmonization and Regulatory Convergence Needed

● Harmonization of pharmacovigilance allow better bigger data sets to be achieved more quickly and can supersede the requirements for PMS studies that are local. Initiatives are already underway, e.g. DQSA (US), 2-D barcodes (EU)

● Pre-agree data cutoffs after which PMS studies can be discontinued

● Real world evidence (RWE) and standards (USP)

● Optimize ROI across multiple jurisdictions to enable greater savings worldwide

Coordinated studies that provide data upon which actions can be taken in multiple jurisdictions concurrently creates predictability

Interchangeability of Biosimilars: A European Perspective here Jan 2017; A ‘Global Reference’ Comparator for Biosimilar Development. Here May 2017An Efficient Development Paradigm for Biosimilars here Aug 2019; Evolution of the EU Biosimilar Framework: Past and Future here Sep 2019

• Value is a Combination of Clinical Outcome and price

Payer/ Provider Recognition of Value

Better clinical outcomes deserve a higher price Same clinical

outcomes at a lower price have value, e.g. generics & biosimilars Older products with

poorer clinical outcomes fall off the marketNet

improvement in health Greater choice

and access

That biosimilars offer the same clinical outcomes at a lower price is yet to be a recognized value, or even basic truth, in the US

• GLOBAL DEVELOPMENT OF ORIGINATOR BIOLOGICS IS AN ACCEPTED NORM

• Both access and affordability of medicines depend on efficient development to accepted clinical standards and norms (e.g. Declaration of Helsinki, ICH1, ICMRA2)

• High standards can seem unaffordable, but lesser standards unacceptable so what is needed is leveraging data cross-jurisdictionally to the right standard – it is the presumed norm for originator medicines and generics

• The highly regulated markets traditionally get the earliest access, but there is increasing intolerance to delayed access for other jurisdictions

• New mechanisms are being sought to facilitate access by minimizing unnecessary repetition of already unnecessary studies, especially clinicals (e.g. WHO Prequalification of Vaccines and Biosimilars), and regulatory hurdles (e.g. Inspections)

Consumer Confidence in All Medicines Depends on Regulatory Consistency Based on Sound Science

1. International Committee for Harmonization http://www.ich.org/home.htm2. International Pharmaceutical Regulators - ICMRA statement about confidence in biosimilar products (for healthcare professionals here), (for patients and the public here)

Trust in regulatory authorities and the basis of their decisions is critical. Yet FDA still adding more demands biosimilars already approved elsewhere... ...and yet more for an IC designation

• https://www.hhs.gov/about/leadership/secretary/speeches/2019-speeches/remarks-to-the-association-for-accessible-medicines.html

• https://www.centerforbiosimilars.com/conferences/aam-access-2019/according-to-azar-those-against-biosimilars-are-simply-on-the-wrong-side-of-history

• https://www.biosimilardevelopment.com/doc/a-second-reformation-returning-biosimilar-regulations-to-scientific-roots-0001

Building on the success of generics, and creating the same kind of success with biosimilars, will require not just efficient approval to enter the market, but also payment systems that can harness new competition. So I want to talk about both elements of a successful generic and biosimilars market today: our efforts at the FDA to foster competition through efficient, safe approvals, and our efforts to create the right incentives, and remove any wrong incentives, to support that competition.

Alex M. Azar IIAssociation for Accessible Medicines 6Feb191

Scott Gottlieb was a very different FDA Commissioner; Alex Azar is a very different Secretary of HHSBOTH SEE/SAW COMPETITION AS THE SOURCE OF INNOVATION IN THE US

According to Azar, "Those Against Biosimilars are, Simply, on the Wrong Side of History“ 1,2

But we have yet to see Administration Policies to match these apparent intentions to enable biosimilars to prosper in the US. Yet some of the answers are already available3

Follow-Up Questions?

Gillian Woollett, MA, DPhilSenior Vice Presidentgwoollett@avalere.com202.207.1320

Biosimilars in the Real-World: Patient and Provider

Perspectives

Who are the stakeholders for biosimilars in the United States?

Payers

Prescribers

Health Systems

Manufacturers

Other Healthcare Providers

Patients

Regulators

Factors Influencing Biosimilar Utilization

Cohen et al. Adv Ther 2017;12(2):2160-2172.

• 1,201 US physicians in specialties that are high biologics prescribers

• 75% trust the FDA approval decisions, but…

• When asked if they believe biosimilars are safe and appropriate for naïve and existing patients….

Uncertainty - Prescribers

Factors Influencing Biosimilar UtilizationUncertainty - Prescribers

Teeple et al. Curr Med Res Opin 2019;35(4):611-617.

• 297 US physicians in specialties that are high biologics prescribers

• Rheumatologists• Dermatologists• Gastroenterologists

• Survey of experience and attitudes around non-medical switching to a biosimilar

63%

42%

44%

33%

Not enough long-term data to be comfortable prescribing

Trust biosimilars are safe

Taking a biosimilar is more risky than an originator

Trust biosimilars are effective for individuals, not just groups

31%

30%

Comfortable with a different FDA process for biosimilars

Comfortable with approval by extrapolation

Factors Influencing Biosimilar UtilizationUncertainty - Prescribers

Adapted from: Teeple et al. Curr Med Res Opin 2019;35(4):611-617.

• When asked about the impact of non-medical switching

67% of surveyed physicians had not heard the specific term “non-medical switching”

Factors Influencing Biosimilar UtilizationUncertainty - Prescribers

Leonard et al. Factors affecting health care provider knowledge and acceptance of biosimilar medicines: a systematic review. J Manag Care Spec Pharm 2019;25(1):102-112.

Global themes:• More comfortable with initiating biosimilars in naïve patients than switching stable patients

• Generally NOT comfortable with indication extrapolation

• Level of biosimilar knowledge varied, but the majority are unsure

Factors Influencing Biosimilar UtilizationUncertainty - Patients

Adapted from: Jacobs et al. Patient attitudes and understanding about biosimilars: an international cross-sectional survey. Patient Prefer Adherence 2016;10:937-948.

• Basic awareness = Defined as reporting at least a general impression of biologics or knew the term “biologic” or “biosimilars”.

Factors Influencing Biosimilar UtilizationUncertainty - Patients

• 1,696 US patients with rheumatoid arthritis, Chrohn’s, ulcerative colitis, psoriasis, psoriatic arthritis currently taking a biologic

Adapted from: Teeple et al. Curr Med Res Opin 2019;35(4):603-609.

Factors Influencing Biosimilar UtilizationUncertainty - Patients

….and other studies

Post-approval studies evaluating comparative safety and effectiveness are critical to generating real-world

evidence to inform clinical practice and policy decisions

OPPORTUNITY FOR EDUCATION

Real-World Evidence

“The FDA uses RWE for regulatory decisions, albeit primarily related to safety. Nevertheless, for some drugs, the demonstration of efficacy has been based on RWE from case series or registries.” – Jarrow et al.

“Multiple converging sub-studies from the same populations, or independent studies combining multiple data sources, could bring real-world data closer to ‘causality’ and could be perceived as acceptable alternatives to randomized trials.” - Greenfield

https://healthpolicy.duke.edu/sites/default/files/atoms/files/rwe_white_paper_2017.09.06.pdfGreenfield. Value in Health 2017;20:1023-4Jarow et al. JAMA 2017;318(8):703.Anglemyer et al. Cochrane Database Syst Rev 2014 Apr 29;(4):MR000034

RWE and Regulatory Use— 21st Century Cures requires FDA to establish a program to evaluate potential use of RWE for approval of new indications or to satisfy post-approval study requirements, label expansion or revision, and benefit/risk profiles

“…on average, there is little evidence for significant effect estimate differences between observational studies and RCTs, regardless of specific observational study design, heterogeneity, or inclusion of studies of pharmacological interventions.” – Anglemyer et al.

Origins in the Gap in EvidenceReal world evidence development initiatives are focused

on expanding evidence effectively, rapidly and cost effectively (e.g., FDA EvGen, PCORI, NIH Collaboratory) G

aps in Evidence

6-7 years & $0.8B-$1.2B on a few thousand patientsCONSEQUENCE

• Great variation between study cohorts and real-world population• Resistance from payers to reimburse for new therapies• Hesitation of physician to prescribe therapy• Undetermined real-world effectiveness of treatments

Phase 1 Phase 2 Phase 3 Phase 420-100 healthy

volunteers100-500 patients with

target condition1000-5000 patients with target condition

Post-marketingresearch and

monitoring

Evidence

Real-world utilization quickly outpaces available clinical evidence

Real-World Data Sources

Study TypesPragmatic Clinical TrialsProspective Observational StudiesRegistry StudiesRetrospective Database StudiesCase Reports

Data SourcesPragmatic or Prospective TrialsAdministrative ClaimsElectronic Health RecordsPatient-Reported/Self-GeneratedRegistries

Strength of Secondary Data

Patient interaction with the U.S. healthcare system generates data

Why is data collected?Payment/billingDocument clinical carePhysician decision supportRecordkeepingRegistriesData provide rich source of information for patient safety evaluations

Platt R, et al. The U.S. Food and Drug Administration's Mini-Sentinel program: status and direction. Pharmacoepidemiol Drug Saf. 2012 Jan;21 Suppl 1:1-8.

Commonly Used Data SourcesAdministrative Claims

Electronic Medical Records

Real-World Data - LimitationsData are usually collected for reasons OTHER THAN research, NOT RANDOMIZED✓Longitudinal: Requires consistent care in one healthcare delivery system and/or insurance plan✓

Market uptake: influences research capability✓✓ Clinical outcomes: may not be readily identified

Coding: Non-specific codes or errors✓Hannan EL. J Am Cardiol Intv. 2008;1(3):211-217.

Patient-Generated DataNot just a PRO Instrument anymore…

Wearable devicesMobile phone applicationsSocial Media

• Mobile app Social Media

• Electronic Health Record• Administrative Claims

• Enriched Data

LINK

Patient Generated Data - Limitations

Subject to recall bias and other reporting errors✓

Must be able to LINK DATA to a longitudinal source (administrative claims) or electronic medical record to be useful✓

✓ Requires active and willing participation

Hannan EL. J Am Cardiol Intv. 2008;1(3):211-217.

Requires careful privacy protections✓

A non-profit, multi-stakeholder, collaborative, scientific public service initiative conducting rigorous post-marketing observational research to monitor biosimilar products and novel biologics for effectiveness and safety in a real-world setting

BBCIC Lines of Inquiry To DateData fitness / infrastructure

Data availability and characterizationo Capture of NDC information on medical claims

Impact of transition from ICD-9 to ICD-10, claims-based algorithms

Descriptive studies

Study design and methods Switching study design and analytic approaches Comparative safety/effectiveness study design and analytic approaches

Protocol-Driven Comparative Safety/Effectiveness Studies

BBCIC Research - Manuscripts

Kent DJ McMahill-Walraven CN, Panozzo CA, et al. Descriptive Analysis of Long- and Intermediate-Acting Insulin and Key Safety Outcomes in Adults with Type 2 Diabetes Mellitus. J Manag Care Spec Pharm.Published online August 2019. https://www.jmcp.org/doi/abs/10.18553/jmcp.2019.19042

McMahill-Walraven CN, Kent DJ, Panozzo CA, et al. Harnessing the Biologicis and Biosimilars Collective Intelligence Consortium to Evaluate Patterns of Care. J Manag Care Spec Pharm. Published online August 2019. https://www.jmcp.org/doi/abs/10.18553/jmcp.2019.19041

Desai RJ, Kim SC, Curtis JR, et al. Methodologic Considerations for Noninterventional Studies of Switching from Reference Biologic to Biosimilars. Pharmacoepidemiol Drug Saf. 2019:1-13. Epub ahead of print.https://onlinelibrary.wiley.com/doi/full/10.1002/pds.4809

Lockhart CM, McDermott CL, Felix T, et al. Barriers and Facilitators to Conduct High-Quality, Large-Scale Safety and Comparative Effectiveness Research: The Biologics and Biosimilars Collective Intelligence Consortium Experience. Pharmacoepidemiol Drug Saf. 2019:1-3. Epub ahead of print.https://onlinelibrary.wiley.com/doi/full/10.1002/pds.4885

BBCIC – Current Projects

Background and RationaleFor over two decades, recombinant human granulocyte colony-stimulating factors (G-CSFs) have been used to treat and prevent chemotherapy-induced neutropenia. Currenty two biosimilar products to reference filgrastim (filgrastim-sndz, filgrastim-aafi), and two biosimilars to reference pegfilgrastim (pegfilgrastim-jmdb, pegfilgrastim-cbqv) have been approved in the US. Building upon a previous BBCIC descriptive analysis, we are starting our first Comparateive Effectiveness Research (CER) project focused on G-CSFs.

The BBCIC has started our FIRST formal Comparative Safety and Effectiveness study of granulocyte-colony stimulating factors (filgrastim, pegfilgrastim) between the originator biologics and their available biosimilars.

COMPARATIVE EFFECTIVENESS RESEARCH – G-CSFs

BBCIC – Current Projects

Background and RationaleA marked increase in the approval of biosimilar products, particularly in cancer therapy, is anticipated as a result of patent expirations for a number of originator biologics. As such, there is a need to generate robust real-world evidence for biosimilar cancer therapeutics. Given the number of biosimilars in oncology expected to be considered for approval in the near future, BBCIC is establishing the necessary resources to do product-or disease-specific comparative effectiveness research.

The BBCIC has begun a new infrastructure project to identify, evaluate, and test potential new data sources to enrich the BBCIC distributed research network (DRN) capabilities in conducting robust, cancer-specific safety and effectiveness research.

ONCOLOGY FEASIBILITY AND DATA FITNESS

Cate Lockhart, MS, PharmD, PhDExecutive Director, BBCICclockhart@bbcic.org703-684-2646

Follow-Up Questions?

Biosimilars in Practice-The Yale New Haven Health System

Experience

Yale New Haven Health At-a-Glance•Five Hospitals

Yale New Haven HospitalBridgeport HospitalGreenwich HospitalLawrence + Memorial HospitalWesterly Hospital

•2,563 Licensed Beds

• 340B and non-340B hospitals• Founding Member and

Service Provider to the Northeast Purchasing Coalition (NPC)

– 14 Members – Aggregation contracting and

utilization projects

What We Originally Thought

Steve Miller, The $250 Billion Potential of Biosimilars, Express Scripts Int’l (Apr. 23, 2013).

YNHHS Take 1-Tbo-Filgrastim (Granix®)• BLA 351(a) approval pathway• Biosimilar in European Union• Only applied for 1 FDA indication and not all of filgrastim indications• At the time No indication for

• BMT• Stem Cell Mobilization• AML

YNHHS: Recommended filgrastim and tbo-filgrastim therapeutically equivalent• Approval: Therapeutic equivalence except in pediatric patients, BMT

patients and mobilization in donors• Limited or no data in these populations

Concerns from Prescribers

• Desire for clinical studies• Immunogenicity• Limited understanding or comfort level with regulatory

requirements/process• Patient Preference• Cost-savings not worth the conversion

YNHHS Take 2: Create Overall Strategy for Biosimilars• Identified the need to set a precedent for the management of all future

Biosimilars• Goal to declare therapeutic equivalence for all biosimilars

• Identified and met with Key Stakeholders• Identified the Oncology Chief Medical Officer as the project Sponsor• Standardized presentation and recommendation presented to all local

P&T Committees, Medical Executive Committees and YNHHS Formulary Integration Committee (FIC)

• Recommendation presented to the YNNHS Oncology Subcommittee and at Oncology Grand Rounds• One-on-One stakeholder discussions occurred as needed

Key Points in Adoption of BiosimilarsWe are already using “biosimilars”

Drugs with significant changes in manufacturing processo Insulino Darbepoetino Immune Globulino Vaccineso Many Biologics

Am Health Drug Benefits.2016;9(9):515-518

YNHHS Formulary Biosimilar Decision/Policy• Biosimilars are considered therapeutically equivalent to the reference

drug for the FDA approved indications • Formulary decisions based on cost and operational considerations • Pharmacy to communicate with key stakeholders prior to formulary

switch • Option to request a formal review

o Must provide additional evidence to support request

What We Are Actually Experiencing

YNHHS/NPC Biosimilar Adoption

NPC contracts: filgrastim, infliximab and pegfilgrastim biosimilars• 100% adoption of filgrastim-sndz (99% Market Share) • 100% adoption of pegfilgrastim-cbqv• 65% adoption of infliximab-abda and infliximab-dyyb

• No current contract for epoetin alfa-epbx

Shane, R, WSJ. August 27, 2019.

Profit and Loss (P&L) Analysis

• Need to collaborate with your Revenue Reporting Department• Analysis Requires:

• Drug: CPT codes, contract cost, common dose, pass-through status Utilization: billed units by payer

• Payer contracts• Decreased drug spend is not always an overall win for the

organization

Infliximab vs. Pegfilgrastim: YNHHS P&L

What are the Barriers to Realizing the Value?• Acceptance by patients and providers

• Need for continued education on the FDA approval process and standards

• Positions of physician organizations• On-going litigation by the innovator manufacturers• Design of innovator novel delivery technologies • Reimbursement• Current Formulary Management Model

What is next for YNHHS?

POST-TEST

LQ1: Of the 23 biosimilars that have been approved in the U.S. to date, how many are available on the market?

a) 4b) 9c) 17d) 23

LQ1: Of the 23 biosimilars that have been approved in the U.S. to date, how many are available on the market?

a) 4b) 9 (slide 11) c) 17d) 23

LQ2: Among U.S. prescribers in specialties where biologics are frequently prescribed, what is the percent who trust biosimilars are safe?

a) Between 10% and 20%b) Between 40% and 50%c) Between 60% and 70%d) Between 80% and 90%

LQ2: Among U.S. prescribers in specialties where biologics are frequently prescribed, what is the percent who trust biosimilars are safe?

a) Between 10% and 20%b) Between 40% and 50% (slide 32)c) Between 60% and 70%d) Between 80% and 90%

LQ3: All of the following are limitations of commonly-used real-world data sources, EXCEPT:

a) Data are typically collected for reasons other than researchb) Market uptake may influence research capabilitiesc) Clinical effectiveness outcomes may be challenging to identifyd) Data are usually randomized

LQ3: All of the following are limitations of commonly-used real-world data sources, EXCEPT:

a) Data are typically collected for reasons other than researchb) Market uptake may influence research capabilitiesc) Clinical effectiveness outcomes may be challenging to identifyd) Data are usually randomized (slide 42)

LQ4: Which is a barrier to biosimilar adoption within a hospital system?

a) Ongoing litigation prevents access to biosimilarsb) Uncertainty around reimbursementc) Design of novel delivery technologyd) Both a and be) All of the above

LQ4: What is a barrier to biosimilar adoption within a hospital system?

a) Ongoing litigation prevents access to biosimilarsb) Uncertainty around reimbursementc) Design of novel delivery technologyd) Both a and be) All of the above (slide 64)

Questions?

Disclaimer

All Faculty in this education session have obtained the appropriate permission to use copyright materials. Sources for all images are provided in citations.